The long term objective of this proposal is to understand mechanisms underlying formation of the eyes in vertebrate embryos. Our focus is on two closely related early steps of eye formation: determination of a retina field and resolution of the single retina field into tow retina primordia. Our research will be carried out primarily with Xenopus embryos which have been made a powerful system for studying eye development by the combination of experimental embryology and molecular biology. Our preliminary studies have contributed to the delineation of early events in retina formation. It is revealed that there is a single retina morphogenetic field in the anterior neural plate. This field resolves into two retina primordia during neurulation. In both Xenopus and chick embryos, the signal for retina field resolution has been shown to come from the prechordal mesoderm. Our preliminary results indicate that Pax-6, a gene capable of causing eye formation in Drosophila, is not sufficient to initiate eye formation in Xenopus embryos, suggesting that additional factors are required for vertebrate eye formation. These studies have thus laid a solid foundation for further investigations of retina field formation and resolution. This application proposes to: 1) study the cellular and molecular mechanisms responsible for the resolution of the retina field into two retina primordia, and 2) isolate genes encoding proteins that interact with Pax-6 and study the synergy between Pax-6 and its interacting molecules in initiating vertebrate eye formation. These studies should advance our understanding of vertebrate eye development in normal embryos and of the etiology of cyclopia in human fetuses, and may provide powerful tools for generating vertebrate eyes.